BXSB and NZB mice are autoimmune, with a 40-60% occurrence of neocortical ectopias. The ectopias, formed during embryonic development, are structurally similar to those seen in brains of dyslexics. Further, dyslexics are 2.5 times more likely to have autoimmune problems than the general population. For these reasons, BXSB and NZB mice have been used to model developmental learning disabilities. On tests of spatial working memory, ectopic BXSBs have poorer scores than non-ectopics. Surprisingly, ectopic BXSB mice are superior to their non-ectopic littermates on the Morris maze (spatial reference memory). NZB ectopics and non-ectopics also differ on the Morris maze, but for this strain ectopics are poorer learners than non-ectopics. Finally, ectopic mice from both strains show poorer performance on discrimination learning. These combined results show that deficits observed for ectopic and non-ectopic mice differ as a function of memory process (reference versus working), type of test (spatial versus nonspatial), and strain. We attribute the strain differences to the fact that in BXSBs, ectopias occur mostly in prefrontal/motor cortex, while in NZBs, ectopias are mainly in somatosensory cortex. Since both prefrontal/motor and somatosensory ectopias occur naturally and are sharply delimited in extent, BXSBs and NZBs provide an ideal preparation with which to study a known anomaly of human neurodevelopment. We propose to build on this developmental disability model by further studying the consequences of ectopias for reference and working memory systems, and spatial and non spatial learning, in both strains. We will also test mice with induced lesions in different cortical locations, and transgenic mice with bilateral ectopias in prefrontal cortex, to address this issue. Moreover, we will assess the effects of environmental enrichment, and an Fl genetic cross between the two strains. These studies speak to the direct consequences of cortical damage on learning and memory in ectopic mice. Evidence also suggests that early cortical damage induces sub-cortical (thalamic) anomalies which may underlie multi-sensory processing deficits in language impaired individuals. We will address this hypothesis by testing auditory, visual, and tactile temporal processing in the BXSB and NZB strains. We predict these strains will be characterized by deficits in sensory processing specific to rapid rates of stimulus presentation, and moreover, that cortical location of ectopias will not significantly influence this effect. In sum, there are sufficient structural similarities between ectopias in mouse and man, and sufficient behavioral similarities between ectopic mice and humans with developmental learning disorders, to lead us to believe that these animal models are rich sources of information and insight about the human condition.